Cisplatin pharmacokinetics in children with cancer.
Cisplatin is an important drug in the treatment of a number of paediatric cancers yet, despite widespread use, there are only very limited data on the pharmacokinetics of the drug in children. Cisplatin pharmacokinetics were studied in 21 patients following a 24 h infusion of 50-120 mg/m2 cisplatin. Total and free platinum (Pt) levels in plasma and Pt in urine, were measured by atomic absorption spectrophotometry. Pharmacokinetic parameters were determined by non-compartmental and compartmental analyses. There was 3-fold interpatient variability in free drug exposure (area under the plasma concentration versus time curve--AUC) for a given surface area-based dose of cisplatin. The mean (+/- SD) pharmacokinetic parameters for free Pt were: AUC 0.47 +/- 0.13 mg/ml.min/100 mg/m2, Vdss 12.5 +/- 2.7 l/m2, t1/2 39 +/- 9 min, Ke 0.019 +/- 0.006 min-1, Clrenal 62 ml/min/m2, Cltotal 233 +/- 455 ml/min/m2, Cpss 0.31 +/- 0.09 microgram/ml. The total free Pt clearance was 1.5-5.8-fold higher (3.4 +/- 1.0) than the glomerular filtration rate (GFR). The renal clearance of cisplatin was not related to GFR and cisplatin was subject to only limited urinary excretion (27% administered dose 0-48 h), indicating that there are other important pathways of clearance beside renal elimination. Patient and treatment heterogeneity precluded the investigation of pharmacokinetic-pharmacodynamic relationships; however, the degree of interpatient pharmacokinetic variability observed suggests that body surface area-based dosing of cisplatin in children is not satisfactory.
Peng
B
B
Cancer Research Unit, Medical School, University of Newcastle upon Tyne, U.K.
English
M W
MW
Boddy
A V
AV
Price
L
L
Wyllie
R
R
Pearson
A D
AD
Tilby
M J
MJ
Newell
D R
DR
D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000493:pharmacokinetics*; D002648:Child; D002675:Child, Preschool; D002945:Cisplatin / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D009369:Neoplasms / Q000097:blood / Q000378:metabolism* / Q000652:urine; D010984:Platinum / Q000097:blood / Q000652:urine
D000970:Antineoplastic Agents; D010984:Platinum; D002945:Cisplatin